Premenstrual syndrome (PMS) is the term in common use to describe the complex of physical and mental symptoms which occur from seven to fourteen days prior to the onset of the menstrual flow. Menstrual discomforts include primary dysmenorrhea which includes painful menstruation and cramping.
Menstruation occurs in women from the age of twelve to thirteen years to, on the average, forty-seven years of age. It occurs at more or less regular intervals, except during pregnancy and lactation. The normal menstrual cycle averages twenty-eight days with some variation based on the woman's age, physical and emotional well being, and other factors. The duration of menstrual flow is variable but usually between three and seven days.
The symptoms of premenstrual syndrome are varied and may range from mild to incapacitating. As many as seventy to ninety percent of all menstruating women have recurrent premenstrual symptoms and as many as twenty to forty percent suffer some degree of temporary mental or physical incapacitation. The psychological symptoms include irritability, lethargy, depression, anxiety, sleep disorders, crying spells, and hostility. The neurological symptoms include headaches, dizziness, fainting, and seizures. Among the physical symptoms are tenderness and swelling in the breasts, constipation, abdominal bloating and cramping, edema in the extremities, less frequent urination, and acne.
The physical, neurological, and psychological symptoms of premenstrual syndrome and dysmenorrhea are a major cause of discomfort to women, and cause substantial loss of time and efficiency in the workplace. The art has attempted to address these problems in a number of nonprescription pharmacological compositions for the treatment of premenstrual and menstrual discomforts without completely successful results.
Most nonprescription products contain either aspirin or acetaminophen as the analgesic. Aspirin and acetaminophen are believed to have equivalent analgesic efficacy for the diminution of headache and other minor pains. Their relative efficacy for relieving premenstrual and menstrual pain has not been determined. Nevertheless, both agents are routinely used for diminishing menstrual pain. Another analgesic frequently recommended is ibuprofen.
Most nonprescription products also contain an antihistamine such as pyrilamine maleate. They also contain diuretics in an amount which would be subtherapeutic if taken separately. The most frequently used diuretics are ammonium chloride, caffeine, and pamabrom.
Among the compositions available to provide relief from one or more of the symptoms of premenstrual syndrome and menstrual discomforts are the commercial products Midol, Midol PMS, Pamprin, and Premensyn PMS. Midol has been marketed as an aspirin tablet containing caffeine and an antispasmodic ingredient. Midol is currently marketed containing acetaminophen and pyrilamine maleate. Midol PMS, Premensyn PMS, and Pamprin all contain acetaminophen, a diuretic, and an antihistamine. All of these active ingredients are considered safe and effective in combination.
Although the commercially available compositions are useful to relieve symptoms of premenstrual syndrome and menstrual discomforts, none are completely effective. Liquid compositions would be desirable because a liquid vehicle speeds the action of both the analgesic and the diuretic and potentiates the active ingredients. Moreover, many persons have difficulty swallowing medications in solid form.
The problem facing the art, however, is that liquids containing analgesic, antihistamine, and diuretic active pharmaceutical agents taste terrible and pharmaceutical chemists have heretofore failed to satisfactorily mask the bitter principals and aftertaste. No patentable liquid products containing this combination of actives are available in the market.
The solid compositions now on the market for relief of premenstrual and menstrual discomfort, including uncoated and chewable tablets, typically taste bitter and metallic. It has always been a difficult challenge for the pharmaceutical chemist in compounding over-the-counter medicines to mask the bitter, metallic, and otherwise unpleasant tastes and lingering aftertastes of many active pharmaceutical agents. This is a particular problem when a liquid dosage form is desirable because in liquid dosage forms the bad taste is usually more apparent than in solid dosage forms including uncoated tablets. It is recognized among pharmaceutical chemists and physicians that patients' compliance with a dosage schedule is of paramount importance for controlling the symptoms and accordingly the organoleptic properties of any medicine must be such that the patient's resistance to following a schedule of administration is minimized.
Among the worst tasting active pharmaceutical agents in over-the-counter medicines, and particularly medicinal liquids, are analgesics, antihistamines, antitussives, sedatives, and others. When these agents are used in combination with one another, the problem is exacerbated. A number of products have failed in the marketplace when patients have refused to take repeat doses even though the active pharmaceutical ingredients were effective for the intended purpose.
Among the ingredients used by pharmaceutical chemists to mask the bitterness of the active pharmaceutical agents are licorice, anise, anethol, glycerrhizins such as ammonium glycyrrhizin, etc., vanillin, ethyl vanillin, methyl salicylate, and menthol and other mild surface anesthetics. The purpose of these flavoring enhancing ingredients is to interact with the bitter principals of the active pharmaceutical agents and to deceive the taste receptors in the mouth. These ingredients have typically fallen short of masking the taste of active pharmaceutical agents, particularly those with strong bitter aftertastes. These aftertastes remain in the mouth long after the initial impact of the medicine which may have been successfully masked.